Direct Antilymphoma Effects on Human Lymphoma Cells of Monotherapy and Combination Therapy with CD20 and HLA-DR Antibodies and 90Y-Labeled HLA-DR Antibodies
| Autor: | Kaylund Chan, Evan Tobin, Bonnie M. Bradt, Sally J. DeNardo, Gerald L. DeNardo |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Time Factors Lymphoma Combination therapy Cell Survival medicine.drug_class medicine.medical_treatment Dose-Response Relationship Immunologic Monoclonal antibody Mice Antigen immune system diseases Cell Line Tumor hemic and lymphatic diseases Animals Humans Medicine Yttrium Radioisotopes Coloring Agents Cell Proliferation CD20 biology business.industry Cell growth Antibodies Monoclonal HLA-DR Antigens Trypan Blue Radioimmunotherapy Antigens CD20 medicine.disease Combined Modality Therapy Treatment Outcome Microscopy Fluorescence Oncology Immunology biology.protein Cancer research Rituximab Lymphoma Large B-Cell Diffuse Radiopharmaceuticals business medicine.drug |
| Zdroj: | Clinical Cancer Research. 11:7075s-7079s |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-1004-0008 |
| Popis: | Purpose: Monoclonal antibodies (mAb) in combination and mAbs combined with a radionuclide (radioimmunotherapy) have both been more effective in patients than mAb monotherapy.Experimental Design: Using assays of cell growth and viability, the dose response and temporal characteristics of CD20 (rituximab) and HLA-DR (Lym-1) mAbs, singly and in combination, and of 90Y-conjugated Lym-1 mAb have been characterized in five human lymphoma cell lines (B35M, Raji, SU-DHL-4, SU-DHL-6, and Ramos) spanning Burkitt's to diffuse large cell lymphoma. Although Ramos had a lower HLA-DR density, these cell lines were otherwise selected because of high cell surface CD20 and HLA-DR abundance. Assays of cell growth and death were done using microscopy and trypan blue dye.Results: Lym-1 and rituximab, used singly, showed direct antilymphoma effects; those of Lym-1 were often more potent than those of rituximab. Combinations of these mAbs were more effective, sometimes synergistic, than either mAb singly, even in more resistant SU-DHL-4 cells. Conjugation of 90Y to Lym-1 also augmented potency in all cell lines and overcame resistance to both Lym-1 and rituximab in Ramos cells.Conclusions: Lym-1 exhibited substantially greater direct antilymphoma effects than rituximab in lymphoma cells in culture. Combination of Lym-1 with rituximab or 90Y increased potency and overcame treatment resistance in lymphoma cells. Greater use of combination therapies of this type to increase potency and range of effectiveness seems likely to improve patient outcome. |
| Databáze: | OpenAIRE |
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